Study Using IMC-A12 (Cixutumumab) With or Without Cetuximab in Patients With Metastatic Colorectal Cancer Who Have Failed a Treatment Regimen That Consisted of a Prior Anti-EGFr Therapy

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Patients with mCRC who have progressed on a prior Anti-EGFr regimen randomized to receive IMC-A12 monotherapy or combination therapy with cetuximab to assess response, survival, durations of response, safety and tolerability as well as pharmacodynamics of IMC-A12 and cetuximab

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Ages Eligible for Study:

18 Years and older (Adult, Senior)

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria

The patient has histologically or cytologically-confirmed colorectal cancer with metastatic disease documented on diagnostic imaging studies

The patient has measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded), measuring ≥ 2 cm on conventional measurement techniques or ≥ 1 cm on spiral computed tomography (CT) scan

The patient has clinical documentation of disease progression during treatment or within 6 weeks after receiving the last dose of a therapeutic regimen for metastatic disease containing an anti-EGFR-component (cetuximab or panitumumab). Toxicity or planned treatment break will not be regarded as adequate evidence of disease progression and such patients will not be eligible for this trial

The patient has received at least one prior standard and/or investigational regimen for metastatic disease

The patient has adequate hepatic function as defined by a total bilirubin ≤ 1.5 x the upper limit of normal (ULN),* and aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x the ULN (or ≤ 5 x the ULN in the presence of known liver metastases)

The patient has adequate coagulation function as defined by international normalized ratio (INR) ≤ 1.5 and partial thromboplastin time (PTT) ≤ 1.5 x the ULN. Patients on full-dose anticoagulation must be on a stable dose of oral anticoagulant or low molecular weight heparin, and if on warfarin must have an INR between 2 and 3 and have no active bleeding or pathological condition that carries a high risk of bleeding (eg, tumor involving major vessels or invading the rectal lumen, or known varices)

Because the teratogenicity of IMC-A12 (cixutumumab) is not known, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation

The patient has the ability to understand and the willingness to sign a written informed consent document

The patient has a tumor that is KRAS wild-type (absence of mutations at codon 12 or 13, as determined by the DxS K-RAS Mutation Kit [PCR-based analysis]).

The patient experienced either a confirmed partial response or stable disease of ≥ 24 weeks duration during prior treatment with a cetuximab- or panitumumab-containing regimen *Except for patients with UGT1A1 promoter polymorphism, ie, Gilbert syndrome, confirmed by genotyping or Invader®UGT1A1 Molecular Assay prior to enrollment. Patients enrolled with Gilbert Syndrome must have a total bilirubin ≤ 3 x ULN. If the patient has liver metastases, total bilirubin must be ≤ 3 x ULN.

Exclusion Criteria

The patient has received chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or has not recovered from adverse events due to agents administered more than 4 weeks earlier. Neurotoxicity, if present, must have recovered to NCI-CTCAE Version 3.0 grade ≤ 2.

The patient is receiving any other investigational agent(s).

The patient has a history of treatment with other agents targeting the IGFR.

The patient has known brain or leptomeningeal metastases.

The patient has a history of primary central nervous system tumors, seizures not well controlled with standard medical therapy, or history of stroke within 6 months prior to randomization.

The patient has a history of allergic reactions attributed to compounds of chemical or biologic composition similar to those of cetuximab or IMC-A12 (cixutumumab).

The patient has poorly controlled diabetes mellitus. Patients with a history of diabetes mellitus are allowed to participate, provided that their blood glucose is within normal range (fasting glucose < 120 mg/dL or below ULN) and that they are on a stable dietary or therapeutic regimen for this condition.

The patient is known to be positive for infection with the human immunodeficiency virus.

The patient is receiving therapy with immune modulators such as cyclosporine or tacrolimus.

The patient has a history of another primary cancer, with the exception of: a) curatively resected nonmelanomatous skin cancer; b) curatively treated cervical carcinoma in-situ; or c) other primary solid tumor curatively resected treated with no known active disease present and no treatment administered for the last 3 years.